PERK-opathies: An Endoplasmic Reticulum Stress Mechanism Underlying Neurodegeneration.
PERK-opathies: An Endoplasmic Reticulum Stress Mechanism Underlying Neurodegeneration.
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DOI：
10.2174/1567205013666151218145431
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发表时间：
2016
影响因子：
2.1
通讯作者：
Abisambra JF
中科院分区：
文献类型：
--
作者：
Bell MC;Meier SE;Ingram AL;Abisambra JF
未折叠蛋白反应（UPR）作为内质网（ER）应激的结果，在维持细胞内稳态中起着至关重要的作用。然而，延长的UPR活性导致细胞死亡。UPR的这种时间依赖性双重功能代表了ER应激导致的适应性和细胞毒性途径。系统性和神经退行性疾病中的慢性UPR激活已被确定为细胞稳态失调的早期迹象。蛋白激酶R样ER激酶（PERK）途径是UPR的三个主要分支之一，也是唯一一个调节蛋白质合成作为适应性反应的途径。延长的PERK活性的特异性鉴定与诸如糖尿病、阿尔茨海默病和癌症的疾病的进展相关，表明PERK在这些疾病的病理学中起作用。对于第一次，术语“PERK病”是用来组这些疾病中PERK介导损害细胞最终在慢性疾病。本文回顾了文献记录系统性疾病与普遍定期审议之间的联系，但特别强调PERK途径。然后，文章报告之间的联系普遍定期审议，更具体地说，PERK，和神经退行性疾病。最后，讨论了治疗角度，其中PERK干预措施可能是慢性神经退行性疾病细胞功能障碍的潜在补救措施。
The unfolded protein response (UPR) plays a vital role in maintaining cell homeostasis as a consequence of endoplasmic reticulum (ER) stress. However, prolonged UPR activity leads to cell death. This time-dependent dual functionality of the UPR represents the adaptive and cytotoxic pathways that result from ER stress. Chronic UPR activation in systemic and neurodegenerative diseases has been identified as an early sign of cellular dyshomeostasis. The Protein Kinase R-like ER Kinase (PERK) pathway is one of three major branches in the UPR, and it is the only one to modulate protein synthesis as an adaptive response. The specific identification of prolonged PERK activity has been correlated with the progression of disorders such as diabetes, Alzheimer’s disease, and cancer, suggesting that PERK plays a role in the pathology of these disorders. For the first time, the term “PERK-opathies” is used to group these diseases in which PERK mediates detriment to the cell culminating in chronic disorders. This article reviews the literature documenting links between systemic disorders with the UPR, but with a specific emphasis on the PERK pathway. Then, articles reporting links between the UPR, and more specifically PERK, and neurodegenerative disorders are presented. Finally, a therapeutic perspective is discussed, where PERK interventions could be potential remedies for cellular dysfunction in chronic neurodegenerative disorders.
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